Overweight and Obese Populations
Prosperous, industrialized countries have a large number of overweight or obese populations. More than half of the adults in the US are overweight (61%) and more than a quarter (26%) are obese. A person who is overweight or obese has an excessive accumulation of fat in the body. One way that excessive accumulation of fat can occur is through consumption of a diet with an energy intake which is greater than the energy expenditure of the body. It is generally agreed that a person is overweight if their body weight exceeds their “desirable weight”, whereas obesity is present if the body weight is 20% or more above the “desirable weight” (Council on Scientific Affairs, 1988, Treatment of obesity in adults, JAMA 260:2547-48). Body mass index (BMI) is a common measure expressing the relationship (or ratio) of weight-to-height. It is a mathematical formula in which a person's body weight in kilograms is divided by the square of his or her height in meters (i.e., wt/(ht)2). The BMI is more highly correlated with body fat than any other indicator of height and weight. Individuals with a BMI of 25 to 29.9 are considered overweight, while individuals with a BMI of 30 or more are considered obese. According to the NIH Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, all adults (aged 18 years or older) who have a BMI of 25 or more are considered at risk for premature death and disability as a consequence of overweight and obesity. These health risks increase as the severity of an individual's obesity increases.
Obesity can be further classified as mild (20-30% overweight), moderate (30-60% overweight) or severe (≧60% overweight). A number of health hazards correlate with moderate and severe obesity, including impairment of both cardiac and pulmonary functions, perturbation of endocrine functions, emotional problems, hypertension, impaired glucose tolerance, non-insulin dependant diabetes mellitus, and hypercholesterolemia. Colonic and rectal cancer are diseases which frequently appear in obese men, and obese women often suffer from endometrial or gallbladder cancer.
The causes of obesity are complex and not fully understood. Obesity can be a result of life-style (i.e. patterns of physical activity and food consumption), or a result of individual genetic propensity.
Methods of Treatment for Weight Loss
The basic principle of treatment of obese or overweight individuals has been establishment of a negative energy balance. A negative energy balance can be accomplished by using one or a combination of three different methods of treatment. The first method of treatment is the reduction of energy intake. This is essentially possible only through dietary treatment, as malabsorption of food cannot be obtained safely either through medication or surgery. The dietary treatment consists of a weight reducing diet as well as a weight maintaining diet.
The second method to achieve a negative energy balance is by an increase in physical activity, which leads to increased energy expenditure. However, in order to obtain a significant amount of weight loss, hours of daily physical activity would be needed. Therefore, physical activity alone plays a minor role in the treatment of obesity but a major role in weight loss maintenance.
The third method to achieve a negative energy balance is through the use of drugs or supplements, either alone or in combination with dietary treatment and/or increased physical activity. The drugs used in the treatment of obesity can be appetite-reducing drugs (sibutramine), drugs that produce malabsorption of fat (orlistat) or carbohydrate (acabose), and thermogenic drugs. A thermogenic drug can be defined as a drug capable of raising the metabolic rate, i.e. increasing the energy expenditure. Known thermogenic drugs are e.g. ephedrine, epinephrine, norepinephrine, isoproterenol, phenylpropanolamin and caffeine (Astrup A., 1986, Thermogenesis in human brown adipose tissue and skeletal muscle induced by sympatomimetic stimulation, Acta Endocrinol. 112, suppl 278:1-32; Hollands, M. A., et al, 1981, A simple apparatus for comparative measurements of energy expenditure in human subjects: the thermic effect of caffeine, Am. J. Clin, Nutr. 34:2291-4). The interest in thermogenic drugs stems from studies which indicate that obesity might be genetically determined, and that the responsible genetic defect relates to a thermogenic defect of the obese person (Dulloo, A. & Miller, D. S., 1989, Ephedrine, caffeine and aspirin: “Over-the-counter” drugs that interact to stimulate thermogenesis in the obese, Nutrition 5:7-9). The term “a thermogenic compound” or “a thermogenically active compound” is understood to mean a compound which is within a living animal capable of raising metabolic rate, i.e. increasing energy expenditure. The term “therapeutically active substance” as used herein is intended to mean any physiologically or pharmacologically active substance that produce a localized or systemic effect in humans.
Treatment of overweight or obese individuals with thermogenic drugs is generally thought to have successful therapeutic value, and as a result there is an interest in the search for new thermogenic compounds.
It has been shown that ephedrine is an effective weight loss agent through its ability to increase thermogenesis and quench appetite. However, the publicity concerning adverse reactions has led to its gradual withdrawal from use. Many companies are now substituting Citrus aurantium for ephedrine in their formulations. (Preuss H. G., et al., 2002, Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview, J. Med., 33(1-4):247-64.)
While many of the technologies mentioned above are useful in losing weight, the problem is keeping the weight off. Often people “yo-yo”, that is, loose large amounts of weight only to gain it back once they discontinue the weight loss program they were on. A reduction in energy gain by 50 kcal/day could offset weight gain in about 90% of the population. This could theoretically be accomplished by walking an extra mile a day (100 kcal), or simply by eating a few bites less of each meal (Hill, J. O., et al., 2003, Obesity and the environment: where do we go from here, Science 299:853-5). Although these simple solutions have been known for many years, the majority of the population is still gaining weight. There is clearly a need for simple and safe methods to achieve satiety and decrease spontaneous food intake, as well as to use safe and effective compounds to increase thermogenesis and lead to weight loss. Therefore, it was of interest to develop a composition containing well-known, harmless food ingredients which achieve a synergistic effect and leads to weight loss.